How can we better understand the developmental nature of cardiovascular disease across the life course and improve the health of people who experience chronic early life stress? In this episode Dr. Nathaniel Jenkins (University of Iowa) interviews lead author Dr. Annemarie Wentzel (North-West University, South African Medical Research Council Unit for Hypertension and Cardiovascular Disease) and expert Dr. Romain Harmancey (The University of Texas Health Science Center at Houston) about the study by Wentzel et al. which found that stress, expressed as a cumulative allostatic load score, impacted the microvasculature, macrovasculature, and central cardiac structure and function on a preclinical level in otherwise healthy emerging adults. The authors also found that the composite allostatic load score was particularly accurate in predicting masked hypertension and pre-diabetes in their study population. The composite allostatic load score incorporates multiple physiological biomarker systems and can offer clinicians an additional tool to use in addressing root causes of chronic stress. Is your hardware for managing stress where it should be developmentally? Listen now and learn more.

A. Wentzel, W. Smith, E. Jansen van Vuren, R. Kruger, Y. Breet, E. Wonkam-Tingang, N. A. Hanchard, and S. T. Chung Allostatic load and cardiometabolic health in a young adult South African population: the African-PREDICT study Am J Physiol Heart Circ Physiol, published February 24, 2025. DOI: 10.1152/ajpheart.00845.2024

The literature shows that the incidence of heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women, but how can researchers study the underlying mechanisms? In our latest episode, Dr. Jonathan Kirk (Loyola University Chicago) interviews lead author Dr. Mei Methawasin (University of Missouri, Columbia) and expert Dr. Glen Pyle (University of Guelph) about the recent study by Methawasin and co-authors investigating sex differences, menopause and HFpEF. The authors created an animal model that resembles HFpEF in women undergoing natural menopause by using 4-vinylcyclohexene dioxide (VCD) to induce “ovary-intact” menopause, combined with the 2hit regimen (HFpEF inducing regimen) to model postmenopausal HFpEF. Combining echocardiography, pressure-volume and single-cell analyses, the authors found that VCD mice, compared to ovariectomized mice and premenopausal mice, have higher testosterone levels compared to other models. By developing this robust phenotype animal model, the authors open new avenues for investigating therapeutic targets in other hormones beyond estrogen alone. Ready to explore the estrobolome, the importance of animal models of human disease, and the complex family of hormones comprising estrogen? Listen now.

Mei Methawasin, Joshua Strom, Vito A. Marino, Jochen Gohlke, Julia Muldoon, Shelby R. Herrick, Robbert van der Piji, John P. Konhilas, Henk Granzier An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency Am J Physiol Heart Circ Physiol, published March 10, 2025. DOI: 10.1152/ajpheart.00575.2024

What is the role of ferroptosis, programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, in the context of ischemic injury related to heart transplantation? In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews authors Dr. Kenneth Liao and Dr. Nandan Mondal (both at Baylor College of Medicine), along with expert Dr. Zachary Kiernan (Virginia Commonwealth University) about the latest study by Li et al. The authors found that prolonged cold storage increases the susceptibility of hearts donated after brain death (DBD) to ferroptotic cell death. In contrast, however, the authors found that warm ischemic injury increased the risk for ferroptotic cell death in hearts donated after circulatory death (DCD). Li et al. found that targeting ferroptosis could be beneficial for optimizing cold preservation for DBD hearts, while interventions for DCD hearts should focus on the early phase of warm ischemia. Heart transplantation is the gold standard therapy for patients with medically refractory advanced heart failure. However, demand greatly exceeds supply of donor hearts. Listen as we discuss the current state of the heart transplantation field and the many challenges it faces.

Shiyi Li, Katherine V. Nordick, Abdussalam E. Elsenousi, Rishav Bhattacharya, Randall P. Kirby, Adel M. Hassan, Camila Hochman-Mendez, Todd K. Rosengart, Kenneth K. Liao, and Nandan K. Mondal Warm-ischemia and Cold Storage Induced Modulation of Ferroptosis Observed in Human Hearts Donated After Circulatory Death and Brain Death Am J Physiol Heart Circ Physiol, published March 28, 2025. DOI: 10.1152/ajpheart.00806.2024